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Published on December 29, 2020
Selinexor (Xpovio) and Dexamethasone Combination Therapy for Relapsed Myeloma
Selinexor (Xpovio), an oral inhibitor of XPO1, and dexamethasone are being studied in combination with several other drugs in an exciting new clinical trial. Follow along as Patient Power co-founder Andrew Schorr speaks with Dr. Cristina Gasparetto, MD, of the Duke Cancer Institute about her presentation of the STOMP clinical trial results at the 62nd Annual American Society of Hematology conference (ASH 2020).
The STOMP trial combines selinexor and dexamethasone with carfilzomib (Kyprolis) for the treatment of relapsed multiple myeloma. Dr. Gasparetto reports that the overall response rate of the trial was 79%; the combination is able to mitigate toxicity; and patients are successfully tolerating long-term therapy. Hear more about this promising news for relapsed myeloma patients!
This program is sponsored by Karyopharm Therapeutics. This organization has no editorial control, and Patient Power is solely responsible for program content.
Transcript | New Combination Therapy for Relapsed Multiple Myeloma
Andrew: Hello and welcome to Patient Power. I'm Andrew Schorr in California but let's shift over to Durham, North Carolina and Duke University and Dr. Cristina Gasparetto who leads the myeloma program at the Duke University Medical Center. Dr. Gasparetto, welcome to Patient Power.
Dr. Gasparetto: Thank you. And thank you for having me here today with you, Andrew.
Andrew: Sure. Dr. Gasparetto, so at the recent American Society of Hematology, or ASH meeting, there was data presented about a fairly new agent, selinexor (Xpovio), used in combination with other drugs. And you were involved in presenting some of that data. So, what is the data showing and what could it mean for some of the sickest myeloma patients?
Can the Combination of Selinexor and Dexamethasone Help Relapsed Multiple Myeloma Patients?
Dr. Gasparetto: Selinexor is an oral, actually the first-in-class, oral inhibitor of Exportin-1, and it was approved in the relapse refractory setting in combination with dexamethasone (Decadron) last year, in 2019. And based on the data of a large phase two study, where patients with failed, mainly other lines of therapy and some of these patients were really refractory to the main classes.
So, their projected lifespan survival was really, definitely not great. And dexamethasone with selinexor was effective in this population of patients, showing an overall response of about 26%. So we knew that this drug in combination with dexamethasone, given by mouth, was effective for this very difficult patient population, right?
What are the Results of the STOMP Study?
And so, shortly after we started to investigate the combination, different combination of selinexor and dexamethasone, with different other agents that we use, other drug, that we use for myeloma. And so, we initiated a very interesting study, the STOMP study, where selinexor-dexamethasone was combined to different drugs. So, different arms. It's actually, right now, we have 15 arms in the STOMP study. No, nine, I'm sorry. Nine arms.
So, one of the arm of the STOMP study was combining selinexor with carfilzomib (Kyprolis) and dexamethasone for patients with heavily pre-treated myeloma. Of course the first part of the study was to try to figure out what was the right dose for this combination, for both selinexor and carfilzomib. And selinexor, when was given in the initial trial in combination with dexamethasone, was given twice a week. On day one and three in combination with dexamethasone.
And one of the problems with that combination, when selinexor is given twice a week, is relatively toxic. There is a fair amount of toxicity, particularly gastrointestinal; nausea, vomiting, weight loss, and others. And so we wanted to see if we could actually use selinexor only once a week in combination with carfilzomib. And so we started at the determined dose and we tried to escalate the dose of carfilzomib, also using the carfilzomib only weekly for convenience. We didn't want to bring the patient twice a week.
And so, we found, we determine, the maximum tolerated dose of the combination and that became our recommended phase two dose for the expansion portion of the study. And we were able to accrue 24 patients. And we follow them for safety and efficacy. And many of these patients, as you can imagine, failed lenalidomide (Revlimid), pomalidomide (Pomalyst), bortezomib (Velcade) and daratumumab (Darzalex), but they were all carfilzomib naive.
And the overall response was great. We had an overall response of about 70 plus percent. Our overall response was 79, no 75%. If we include also the clinical benefit, was up to 79%. And we had actually 33%, one-third of patients, were able to achieve more than VGPR, very good partial response.
And in terms of safety, it was also very interesting because when we started to use the combination, the selinexor only once a week, we were able to mitigate some of the toxicity that we saw with the twice a week administration. So, clearly, there was the same kind of toxicity, but less. So, we were very pleasantly surprised because the toxicity was clearly mitigated, and patients were able to tolerate therapy for a prolonged period of time.
Andrew: Dr. Gasparetto, so as I understand it, you've been looking for better options for people who've had many prior therapies and are not doing well with their myeloma. And it seems like this research, with the addition of selinexor as a new class of medicine and other medicines you have, changing the dosing, may be less frequent, lower dosing, you're getting effectiveness that people can take the medicines for extended times and do better than they would otherwise.
How Is Selinexor Administered? What Are its Unique Characteristics?
Dr. Gasparetto: Absolutely. Yes. I think as you mentioned, it’s a new target, it’s a new class, it’s given by mouth once a week so it’s kind of convenient. And so we are investigating many other combinations. I'm very intrigued by the oral combination, like the selinexor-pomalidomide for patient convenience, of course.
There are some characteristics of this drug that I like. First of all, we have some good data on the other, the phase three study, the BOSTON study, showing that it seems to be very effective for patients with high-risk myeloma, based on cytogenetics. So including the deletion 17, some of the 1q amplification. So we love that.
There is also brain penetration. So, myeloma doesn't go generally to the brain but there are occasionally patients presenting with localized plasmacytomas. And there is a barrier, a penetration. So we like that there is a tissue penetration. So I think it’s going to be a very interesting drug. Also safe for patient with renal compromisation. We have a lot of these patients that unfortunately are unable to participate to clinical trial because the renal function. But it seems very safe also in this population of patients.
So, I think is a new drug that I hope the community physician can start to use more now that they have more data with these different combinations, we're generating more data. But definitely, I love this drug.
I had now several years of experience, and I have to say that I had a lot of success stories. And sometimes I push hard the first month. I call the loading month. And then if I achieve a good response I decrease, based on the toxicity. And that's the reason why some patients were able to sustain therapy for a prolonged period of time.
Andrew: Dr. Cristina Gasparetto from Duke University and leading the myeloma program there. Thank you for the research you're doing and really refining myeloma treatment to help more people live longer and live better. Thank you for being with us.
Dr. Gasparetto: Thank you. Thank you for inviting me today. Thank you, Andrew.
Andrew: I'm Andrew Schorr. Remember, knowledge can be the best medicine of all.